The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein

Choongho Lee; Han Ma; Julie Qi Hang; Vincent Leveque; Ella H. Sklan; Menashe Elazar; Klaus Klumpp; Jeffrey S. Glenn

doi:10.1016/j.virol.2011.03.026

The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein

Choongho Lee, Han Ma, Julie Qi Hang, Vincent Leveque, Ella H. Sklan, Menashe Elazar, Klaus Klumpp, Jeffrey S. Glenn

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

Abstract

The hepatitis C virus (HCV) non-structural (NS) 5A protein plays an essential role in the replication of the viral RNA by the membrane-associated replication complex (RC). Recently, a putative NS5A inhibitor, BMS-790052, exhibited the highest potency of any known anti-HCV compound in inhibiting HCV replication in vitro and showed a promising clinical effect in HCV-infected patients. The precise mechanism of action for this new class of potential anti-HCV therapeutics, however, is still unclear. In order to gain further insight into its mode of action, we sought to test the hypothesis that the antiviral effect of BMS-790052 might be mediated by interfering with the functional assembly of the HCV RC. We observed that BMS-790052 indeed altered the subcellular localization and biochemical fractionation of NS5A. Taken together, our data suggest that NS5A inhibitors such as BMS-790052 can suppress viral genome replication by altering the proper localization of NS5A into functional RCs.

Original language	English
Pages (from-to)	10-18
Number of pages	9
Journal	Virology
Volume	414
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2011.03.026
State	Published - 25 May 2011

Keywords

Anti-HCV compounds
BMS-790052
Hepatitis c virus
NS5A inhibitor
NS5A protein
Replication complex

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.virol.2011.03.026

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title = "The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein",

abstract = "The hepatitis C virus (HCV) non-structural (NS) 5A protein plays an essential role in the replication of the viral RNA by the membrane-associated replication complex (RC). Recently, a putative NS5A inhibitor, BMS-790052, exhibited the highest potency of any known anti-HCV compound in inhibiting HCV replication in vitro and showed a promising clinical effect in HCV-infected patients. The precise mechanism of action for this new class of potential anti-HCV therapeutics, however, is still unclear. In order to gain further insight into its mode of action, we sought to test the hypothesis that the antiviral effect of BMS-790052 might be mediated by interfering with the functional assembly of the HCV RC. We observed that BMS-790052 indeed altered the subcellular localization and biochemical fractionation of NS5A. Taken together, our data suggest that NS5A inhibitors such as BMS-790052 can suppress viral genome replication by altering the proper localization of NS5A into functional RCs.",

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author = "Choongho Lee and Han Ma and Hang, {Julie Qi} and Vincent Leveque and Sklan, {Ella H.} and Menashe Elazar and Klaus Klumpp and Glenn, {Jeffrey S.}",

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AU - Sklan, Ella H.

AU - Elazar, Menashe

AU - Klumpp, Klaus

AU - Glenn, Jeffrey S.

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AB - The hepatitis C virus (HCV) non-structural (NS) 5A protein plays an essential role in the replication of the viral RNA by the membrane-associated replication complex (RC). Recently, a putative NS5A inhibitor, BMS-790052, exhibited the highest potency of any known anti-HCV compound in inhibiting HCV replication in vitro and showed a promising clinical effect in HCV-infected patients. The precise mechanism of action for this new class of potential anti-HCV therapeutics, however, is still unclear. In order to gain further insight into its mode of action, we sought to test the hypothesis that the antiviral effect of BMS-790052 might be mediated by interfering with the functional assembly of the HCV RC. We observed that BMS-790052 indeed altered the subcellular localization and biochemical fractionation of NS5A. Taken together, our data suggest that NS5A inhibitors such as BMS-790052 can suppress viral genome replication by altering the proper localization of NS5A into functional RCs.

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The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein

Abstract

Keywords

UN SDGs

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